Neural stem cell-derived exosomes regulate cell proliferation, migration, and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia.

Our previous study found that mouse embryonic neural stem cell (NSC)-derived exosomes (EXOs) regulated NSC differentiation via the miR-9/Hes1 axis. However, the effects of EXOs on brain microvascular endothelial cell (BMEC) dysfunction via the miR-9/Hes1 axis remain unknown. Therefore, the current study aimed to determine the effects of EXOs on BMEC proliferation, migration, and death via the miR-9/Hes1 axis. Immunofluorescence, quantitative real-time polymerase chain reaction, cell counting kit-8 assay, wound healing assay, calcein-acetoxymethyl/propidium iodide staining, and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs. EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. The overexpression of miR-9 promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. Moreover, miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death. Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death. Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice. Meanwhile, EXO treatment improved cerebrovascular alterations. NSC-derived EXOs can promote BMEC proliferation and migration and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions. Therefore, EXO therapeutic strategies could be considered for hypoxia-induced vascular injury. © 2024 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.

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Xiaojun Deng, Xiaoyi Hu, Shang Wang, Hui Zhao, Yaqin Wei, Jiaqi Fu, Wenhui Wu, Jinming Liu, Caicai Zhang, Lili Wang, Ping Yuan. Neural stem cell-derived exosomes regulate cell proliferation, migration, and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia. Animal models and experimental medicine. 2024 Feb;7(1):24-35

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PMID: 38369683

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